A propellant filling apparatus

ABSTRACT

A propellant filling apparatus ( 10 ) comprising a filling booth ( 11 ) for receiving within it one or more containers for filling with a propellant; a propellant inlet ( 12 ) to the filling booth ( 11 ) that is capable of supplying propellant into one or more containers within the filling booth ( 11 ) from a propellant supply; an inert gas inlet ( 13 ) supplying inert gas from an inert gas supply ( 14 ) into the filling booth ( 11 ), a discharge outlet ( 16 ) from the filling booth ( 11 ); an extraction fan ( 17 ) that is capable of adjusting its fan speed to maintain the pressure of gas in the filling booth ( 11 ) to be lower than atmospheric pressure; and an oxygen detector ( 27 ) that is capable of detecting levels of oxygen in the filling booth ( 11 ) and triggering circulation of inert gas in the filling booth ( 11 ) when the level of oxygen in the filling booth ( 11 ) falls below an oxygen threshold level.

This invention relates to a propellant filling apparatus and its methodof operation.

Propellants are widely use in the pharmaceutical, household and cosmeticaerosol industries.

In the pharmaceutical industry, inhalation aerosols also known asMetered Dose Inhalers (MDIs) provide an effective method of deliveringmedication in an atomised form. Propellants are used to force themedication out of a container through a nozzle or similar atomisingoutlet. The invention as defined herein is of particular benefit in thehandling of propellants in MDI filling apparatuses. It is additionallyof benefit in other propellant filling situations.

Chlorofluorocarbons (CFCs) previously were often used as propellants butsince the Montreal Protocol came into force in 1989, they have beenreplaced in nearly every country due to the negative effects CFCs haveon the Earth's ozone layer. Whilst many household and consumer aerosolshave transitioned to hydrocarbon (HC) propellants, the particularrequirements of the medical aerosols sector, and especially inhalationaerosols such as asthma inhalers, require the use of the non-flammablehydrofluorocarbons (HFCs): either HFC 134a (1,1,1,2,-tetrafluoroethane)or HFC 227 (1,1,1,2,3,3,3-heptafluoropropane) or combinations of thetwo.

There is growing concern that many HFCs have high global warmingpotential (GWP) and also an interest in adopting reduced-GWP HFCs wherepossible. Examples of HFCs that have relatively low global warmingpotential when compared to other HFCs include R32 (difluoromethane),R152a (1,1-difluoroethane), R1234yf (1,1,1,2-tetrafluoropropene),R1234ze(E) and (Z) (1,1,1,3-tetrafluoropropene) and the HCFC R1233zd(E)(trans-1-chloro-3,3,3-trifluoropropene). However with the exception ofR1233zd(E) all of these reduced GWP fluids are flammable to a degree.This flammability creates challenges, in particular with regard tostorage and also to the handling of the propellant in productionsituations, particularly in so-called “current good manufacturingpractice” (cGMP) environments. The invention seeks to address suchproblems.

According to an aspect of the invention, there is provided a propellantfilling apparatus comprising a filling booth for receiving within it oneor more containers for filling with a propellant; a propellant inlet tothe filling booth that is capable of supplying propellant, for filinginto one or more containers within the filling booth, from a propellantsupply; an inert gas inlet supplying inert gas from an inert gas supplyinto the filling booth; a discharge outlet from the filling booth; anextraction fan that is capable of adjusting its fan speed to maintainthe pressure of gas in the filling booth to be lower than atmosphericpressure outside the filling booth; and an oxygen detector that iscapable of detecting levels of oxygen in the filling booth andtriggering circulation of inert gas in the filling booth when the levelof oxygen in the filling booth attains or exceeds an oxygen thresholdlevel that is proportional to the maximum oxygen concentration of thepropellant.

In use the apparatus of the invention permits the controlledintroduction of an inert gas into an enclosed volume (i.e. the fillingbooth) containing a flammable component such as but not limited to apropellant. This reduces the oxygen level in the enclosed volume andtherefore reduces the risk of an explosion or ignition event occurring.In this regard, for a variety of reasons ambient air may leak into thefilling booth, with the result that oxygen levels may rise above asafety threshold, giving rise to an explosion or ignition risk. Theinvention prevents such increases in oxygen content from occurring.

As used herein references to “oxygen levels” are to concentrations ofoxygen in e.g. the enclosed volume defined by the filling booth.Similarly, references to levels of inert gas and levels of propellantare references to concentration levels within e.g. a volume such as thatof the filling booth.

The propellant filling apparatus as defined above is furtheradvantageous because it controls the introduction of inert gas to onlythose times in a filling process that have the highest risk (for exampleduring start up and shut down) and also controls the levels of inertgas. This leads to minimising of the consumption of the inert gas,thereby reducing costs. An additional advantage is that through use ofthe apparatus the volume of a production area that is supplied withinert gas is kept to a minimum, thereby improving operator safety.

Furthermore the extraction fan, by controlling the pressure in the boothsuch that it is lower than atmospheric pressure, ensures that there isno leakage of inert gas or propellant from the booth into the room orfactory space where the apparatus is located. This is desirable since itprotects operators in the room from, for example, oxygen depletion dueto increases in amounts of inert gas in the room.

It is preferable if the propellant filling apparatus further comprises apropellant detector that is capable of detecting levels of propellant inthe filling booth and triggering the circulation of inert gas in thefilling booth when the level of propellant in the filling booth risesabove a propellant threshold level.

The propellant detector provides an additional means of ensuring thatthe level of propellant in the filling booth does not exceed a levelwhich may create a risk of explosion or ignition in the filling booth.

The propellant may be a flammable gas. The flammable propellant willpreferably comprise one or more of R32 (difluoromethane), R152a(1,1-difluoroethane), R1234yf (1,1,1,2-tetrafluoropropene), R1234ze(E)and (Z) (1,1,1,3-tetrafluoropropene) and the HCFC R1233zd(E)(trans-1-chloro-3,3,3-trifluoropropene). More preferably the propellantwill comprise R32 and/or R152a and more preferably will consistessentially of R32 and/or R152a. By consisting essentially of we meanthat the propellant contains at least 95% by weight, more preferably 98%by weight and even more preferably at least 99% by weight of thespecified propellant component(s). The propellant preferably has aglobal warming potential (GWP) of below 1000, more preferably below 700and especially preferably below 150.

The propellant may include other non-propellant species such assolvents, surfactants, lubricants and other excipients commonly used inthe art including but not limited to ethanol, glycerol and surfactantssuch as oleic acid, lecithin and polyvinylpyrrolidone (PVP). Further,the propellant may include minor quantities of one or more activepharmaceutical ingredients (APIs) either in solution or suspension inthe propellant.

References to the term “propellant” in the description hereof refertypically to unadulterated propellants (such as R32 and/or R152a). Suchpropellants may alternatively be present in mixtures containing, forexample, components such as polar excipients/co-solvents such asethanol, drugs and surfactants typically in small amounts as would beunderstood by the person of skill in the art.

It is beneficial to the environment to use a propellant (or propellantmixture) comprising R32 and/or R152a because it has an ozone depletionpotential of zero, and a lower global warming potential and a shorteratmospheric lifetime than several other propellant types.

The inert gas may be any non-flammable inert gas with low GWP includingnitrogen, and argon.

It is advantageous to use nitrogen for oxygen depletion because it isinert, widely available, and relatively inexpensive compared to otherinert gases. Other gases may however be employed for this purpose ifdesired.

It is preferable if the oxygen threshold level is 9.8%. For increasedsafety, it is further preferred to maintain an oxygen threshold level of7.8% or lower.

It is advantageous if the propellant filling apparatus includes acontroller for controlling the temperature of the inert gas supplyand/or for controlling the humidity of the inert gas supply.

The ability to control the temperature and humidity of the gas supplywithin a room is desirable to satisfy clean room requirements in thepharmaceutical industry and several other industries in which theinvention may be used.

Conveniently, the speed of the extraction fan may be controlled using apressure controller that measures the pressure of gas in the fillingbooth (or is operatively connected to a pressure measuring device thatgenerates one or more signals, such as electrical or other physicalsignals, that indicate the measured pressure and are fed as inputs tothe pressure controller) and compares the measured pressure withatmospheric pressure in the vicinity of and external to the fillingbooth. Preferably the pressure controller also performs an indicatorfunction whereby an operator of the apparatus may visually assess thegas pressure in the filling booth.

It is advantageous if the propellant filling apparatus satisfies cGMPrequirements.

According to another aspect of the invention, there is provided a methodof operating a propellant filling apparatus, the method comprising thesteps of filling one or more containers in a filling booth with apropellant; supplying an inert gas into the filling booth; adjusting thefan speed of an extraction fan to maintain a lower pressure in thefilling booth than atmospheric pressure outside the filling booth;detecting levels of oxygen in the filling booth; and circulating theinert gas in the filling booth when the detected level of oxygen in thefilling booth attains or exceeds a threshold level corresponding to themaximum oxygen concentration of the propellant.

As used herein the term “filling” is not necessarily intended to implycomplete filling of a container or single-step filling; and on thecontrary may include e.g. partial filling, stepwise filling involving anumber of filling stages, over-filling and/or purging of thecontainer(s).

It is advantageous if the method further comprises the step of detectingthe level of inert gas in the filling booth.

There now follows a description of preferred embodiments of theinvention, by way of non-limiting example, with reference being made toaccompanying FIG. 1 that is a schematic representation of an embodimentof a propellant filling apparatus according to the invention.

FIG. 1 depicts in schematic form a propellant filling apparatus 10comprising a filling booth 11. The filling booth 11 may be constructedfrom e.g. five mutually orthogonal walls and a floor that are joinedalong adjacent edges to define a cuboidal volume inside which filling ofcontainers with propellant is intended to take place. One or more of thefilling booth walls may be equipped with an openable door or otheropening permitting human access to the cuboidal space. One or morefurther apertures may be provided in order to permit the infeed of emptycontainers and the egress of filled containers. The characteristics ofthe filling booth and substantial parts of the filling apparatus will beknown to the person of skill in the art and do not require detaileddescribing herein.

In use the filling booth 11 receives one or more containers, notdepicted, within it for filling with a propellant. In the manufacture ofMDIs, the one or more containers is for holding a mixture of insolublemedication suspended in liquefied, pressurised propellant. The fillingof other types of containers is also possible using apparatuses andmethods according to the invention.

The filling booth 11 is typically located in a clean room or factoryspace that satisfies cGMP requirements. Additionally, as mentioned, thepropellant filling apparatus 10 itself in most embodiments of theinvention satisfies cGMP requirements.

The filling booth 11 has a propellant inlet 12, that is capable ofsupplying propellant for filling into the one or more containers from apropellant supply (labelled “R152a leakage IN” in FIG. 1, although asnoted the invention is not limited to the use of R152a, or indeed asingle substance, as the propellant), and an inert gas inlet 13supplying inert gas from an inert gas supply 14 such as but not limitedto a gas generator, a cylinder or gas tank into the filling booth 11.The inert gas inlet 13 is a gas supply line that connects the inert gassupply 14 to the filling booth 11.

In FIG. 1 the inert gas supply 14 is labelled “N₂ supply”. As explainedherein the invention is not limited to the use of nitrogen as the inertgas, although in many situations this gas is preferred.

The filling booth 11 is capable of working using e.g. powder-fill,suspension-fill and cold-fill techniques. These techniques are known tothe person of skill in the art for filling the containers withpropellant and other substances forming the contents of, for example, anMDI.

In the preferred embodiment of the invention, the propellant is R32and/or R152a. In other embodiments of the invention any of a variety ofpropellants, including in some cases non-HFC propellants, may be used.

As mentioned, the inert gas can be nitrogen. Nitrogen can be suppliedfrom, for example, a gas generator such as but not limited to a nitrogenpressure swing absorption (PSA) system. The nitrogen produced from thePSA system preferably is filtered to the correct particulate levelbefore it is allowed to be released into the propellant fillingapparatus 10.

Other sources of inert gas, especially but not limited to nitrogen, arepossible within the scope of the invention.

A discharge outlet 16 allows gas to leave the filling booth 11 and bedischarged outside of the propellant filling apparatus 10.

The filling booth 11 is connected by way of the discharge outlet 16 toan extraction fan 17 which is capable of adjusting its fan speed tomaintain the pressure of gas in the filling booth 11 to be lower thanatmospheric pressure outside the filling booth 11.

An air inlet 18 in the illustrated embodiment also connects to thefilling booth 11 via the inert gas inlet 13. The air inlet 18 iscontrolled by a valve V1 which is further described below. The air inlet18 allows air from outside the propellant filling apparatus 10 (andlabelled “Air from room IN” in FIG. 1) into the filling booth 11.

As illustrated in FIG. 1, a pipe 19 allows gas to leave the fillingbooth and depending on the settings of various valves that are describedbelow connects to either (i) the extraction fan 17 for discharging viathe discharge outlet 16 or (ii) a recirculation pipe 21 which connectsto the inert gas inlet 13 leading into the filling booth 11.

A recirculation fan 22 is located in the recirculation pipe 21. When therecirculation fan 22 turns on, inert gas and other gases removed fromthe filling booth 11 via pipe 19 enter the recirculation pipe 21 and arereturned to the filling booth 11. In other words, the recirculation fan22 recirculates the inert gas which has been released by the inert gassupply 14 into the filling booth 11.

The propellant filling apparatus 10 comprises valves V1 to V5 whichcontrol the passage of gas or air in particular directions as follows:

-   -   Valve V1, located in the air supply inlet 18, allows/stops        inflow of atmospheric air into the filling booth 11;    -   Valves V2 and V5, located in the recirculation pipe 21,        allow/stop recirculation of inert gas;    -   Valve V3, located in the inert gas inlet 13, allows/stops the        flow of inert gas from the inert gas supply 14; and    -   Valve V4, located in the discharge outlet 16, allows/stops        discharge of air from the filling booth 11 via the extraction        fan 17

The speed of the extraction fan 17 is controlled using a pressurecontroller. As illustrated in FIG. 1, the pressure controller can be apressure indicator controller (PIC) 23 which measures and indicates thepressure of gas in the filling booth 11 and allows the speed of theextraction fan 17 to be adjusted via, for example, a Variable SpeedDrive (VSD) 24 to maintain the filling booth 11 pressure belowatmospheric pressure outside the filling booth 11. The VSD 24 may beconnected to the PIC 23 via a pilot line 26 indicated in dotted lines inFIG. 1. Details of the nature and operation of the VSD 24 will be knownto the person of skill in the art and therefore do not need to bedescribed in detail herein.

The propellant filling apparatus 10 in accordance with the inventionoperates within a safety margin determined by the Maximum OxygenConcentration (MOC) specific to the propellant (or propellant mixture)under consideration. Any concentration below this level can beconsidered safe. This is because, as mentioned above, if the oxygenlevel attains or exceeds the MOC there is a risk (which may be a highrisk) of an explosion or a fire event occurring.

The basic formula for calculating the MOC is:

LEL×Moles O₂=MOC

wherein LEL is the Lower Explosion Limit for the flammable propellant inquestion; and Moles O₂ is the number of moles of oxygen which will reactwith 1 mole of flammable propellant, based upon the stoichiometricequation of combustion.

As an added safety measure, the Recommended Maximum Oxygen Concentration(RMOC) is calculated at 80% of the MOC.

Taking the exemplary embodiment in which the propellant is R152a and theinert gas is nitrogen, the following steps are taken for calculating theRMOC:

1) Determine the stoichiometric number of moles of oxygen required tocompletely burn 1 mole of R152a with the chemical formula CH₃CF₂H.

C₂F₂H₄+2.5O₂→2CO₂+2HF+H₂O

From the above equation, 2.5 moles of oxygen are required to burn 1 moleof R152a.

2) Multiply the number of moles of oxygen obtained in Step 1 by the LELfor R152a. This is the MOC.

The LEL of R152a is 3.9%.

Thus the MOC=3.9×2.5=9.75% in the case of R152a.

The propellant filling apparatus 10 further comprises an oxygen detector27. The output signal 29 from the oxygen detector determines theposition of the inert gas flow control valve V3 under the control ofpressure controlled valve (PCV) elements represented by numeral 28.There are many different ways in which the oxygen detector 27 canmeasure oxygen level and the invention includes measuring oxygen usingapparatuses which include zirconia-based sensor elements and/or rely onphysical effects such as electrochemical/Galvanic phenomena, infraredenergy, ultrasonic energy or laser energy.

The propellant filling apparatus 10 may also comprise a propellantdetector 31 that is capable of detecting levels of propellant in thefilling booth 11. The propellant detector may be specific to one or moreparticular kinds of propellant, as indicated by the labelling in FIG. 1.Other types of propellant detector also are possible within the scope ofthe invention.

The propellant filling apparatus 10 may comprise a controller (not shownin the drawing) for controlling the temperature of the inert gas supply14.

When the apparatus 10 is not in use, valves V1, V3 and V5 are closedwhereas valves V2 and V4 are open.

When an operator desires to use the filling booth 11 to fill one or morecontainers with propellant, the operator temporarily enters or otherwiseaccesses the filling booth 11 via, for example, the openable door asdescribed above to place the containers in the filling booth 11.

The propellant filling apparatus 10 is activated with the result thatpropellant enters the filling booth 11 via the propellant inlet 12. Mostof the propellant is filled into the containers using e.g. an indexablefilling head but some propellant spillage typically occurs.

To prevent the oxygen level in the filling booth from rising above theMOC and thereby risking the initiation of combustion of the propellant,the operator by opening valve V3 adds inert gas from the inert gassupply into the filling booth 11. Instead of a manual intervention by anoperator, an automated control regime can alternatively be implementedto open the valve V3 and/or the other controllable elements describedherein, including valves V1, V2, V4 and V5. The elements of a suitablecontrol arrangement will be known to the person of skill in the art.

Indeed all references herein to manual intervention by an operator canbe considered alternatively to be suitable for completion using anautomated system.

When the operator of the propellant filling apparatus 10 switches on theextraction fan 17, but the recirculation fan 22 is not yet switched on,leakage of air takes place into the filling booth 11. This causes theoxygen level in the vicinity of the propellant in the filling booth 11to rise, potentially to dangerous levels as described herein.

When however the operator opens valve V3 to allow inert gas to enter thefilling booth 11, the extraction fan 17 activates and adjusts its speedto maintain the required filling booth pressure to lower than theatmospheric pressure outside the filling booth 11. This causes purgingof the filling booth 11 with inert gas. This reduces the oxygenconcentration to safe levels.

Purging is continued for as long as necessary in order to achieve theaforementioned effect.

While effecting filling of the containers within the filling booth 11with propellant, if required, the operator (or, if present, an automaticcontrol arrangement) can open valve V1 to effectively allow a largerinflow of air into the filling booth 11. The inert gas inflow thenincreases through operation of components V3 and 28 with the aim ofmaintaining the oxygen concentration at or below the oxygen thresholdlevel, i.e. the MOC or more preferably the RMOC as explained. The fanspeed of the extraction fan 17 also increases to maintain a lowerpressure than atmospheric pressure within the filling booth 11. Thismode ensures that propellant leaks are not concentrated in the fillingbooth 11, due to the recirculation effect. This could also be achievedwithout adding extra air inflow by opening valve V1, increasing theinert gas inflow from the inert gas supply 14 and increasing the speedof the extraction fan 17.

The oxygen detector 27 is capable of detecting levels of oxygen in thefilling booth 11 and triggering circulation of inert gas in the fillingbooth 11 when the level of oxygen in the filling booth 11 falls belowthe MOC or preferably the RMOC.

When the oxygen detector 27 senses that the level of oxygen in thefilling booth 11 has reached or fallen below the oxygen threshold level,the filling booth 11 is considered purged. This triggers therecirculation fan 22 to start and valve V5 is opened so that there isrecirculation of the inert gas within the filling booth 11. This leadsto control of the overall quantity of inert gas required to maintain therequired low level of oxygen concentration.

When purging is no longer needed, in other words when there is no longera supply of propellant for filling containers within the filling booth11, valves V2, V3 and V5 close and the recirculation fan 22 is stopped.Valves V1 and V4 open so that air from outside the propellant fillingapparatus can displace the inert gas. This step is desirable at the endof the run of the filling operation or if for example an operator needsto access the filling booth 11.

The propellant filling apparatus 10 according to the invention givesrise to numerous advantages, as set out above, compared with the priorart. It is expected to make a significant contribution both to thesafety of propellant filling manufacturing and to reducing the cost ofmanufacture.

For the avoidance of doubt it Is emphasised that the invention includeswithin its scope both apparatus as claimed and described herein; andmethods as described and claimed herein. Such methods may as noted beput into effect through the intervention of a human operator, or throughthe operation of automated control elements. In the latter case thecontrol elements may operate on the basis of fixed logic such asfirmware; or one or more of them may be under the control of aprogrammable device such as a microprocessor, personal computer or linecontroller.

Preferences and options for a given aspect, feature or parameter of theinvention should, unless the context indicates otherwise, be regarded ashaving been disclosed in combination with any and all preferences andoptions for all other aspects, features and parameters of the invention.

The listing or discussion of any apparently prior published document orapparatus in this specification should not necessarily be taken as anacknowledgement that the document or apparatus is part of the state ofthe art or is common general knowledge.

1. A propellant filling apparatus (10) comprising a filling booth (11)for receiving within it one or more containers for filling with apropellant; a propellant inlet (12) to the filling booth (11) that iscapable of supplying propellant, for filing into one or more containerswithin the filling booth (11), from a propellant supply; an inert gasinlet (13) supplying inert gas from an inert gas supply (14) into thefilling booth (11); a discharge outlet (16) from the filling booth (11);an extraction fan (17) that is capable of adjusting its fan speed tomaintain the pressure of gas in the filling booth (11) to be lower thanatmospheric pressure outside the filling booth (11); and an oxygendetector (27) that is capable of detecting levels of oxygen in thefilling booth (11) and triggering circulation of inert gas in thefilling booth (11) when the level of oxygen in the filling booth attainsor exceeds an oxygen threshold level that is proportional to the maximumoxygen concentration of the propellant.
 2. A propellant fillingapparatus (10) according to claim 1, further comprising a propellantdetector (31) that is capable of detecting levels of propellant in thefilling booth (11) and triggering circulation of inert gas in thefilling booth (11) when the level of propellant in the filling booth(11) rises above a propellant threshold level.
 3. A propellant fillingapparatus (10) according to claim 1 supplying in use a said propellant,wherein the propellant is a flammable gas.
 4. A propellant fillingapparatus (10) of claim 3 wherein the flammable gas comprises one ormore of R32 (difluoromethane), R152a (1,1-difluoroethane), R1234yf(1,1,1,2-tetrafluoropropene), R1234ze (E) and (Z)(1,1,1,3-tetrafluoropropene) and the HCFC R1233zd(E)(trans-1-chloro-3,3,3-trifluoropropene).
 5. A propellant fillingapparatus (10) of claim 3 wherein the flammable gas consists entirely ofR32.
 6. A propellant filling apparatus (10) of claim 3 wherein theflammable gas comprises at least 95 weight % of R32.
 7. A propellantfilling apparatus (10) of claim 3 wherein the flammable gas comprises atleast 98 weight % of R32.
 8. A propellant filling apparatus (10) ofclaim 3 wherein the flammable gas comprises at least 99 weight % of R32.9. A propellant filling apparatus (10) of claim 3 wherein the flammablegas consists entirely of R152a.
 10. A propellant filling apparatus (10)of claim 3 wherein the flammable gas comprises at least 95 weight % ofR152a.
 11. A propellant filling apparatus (10) of claim 3 wherein theflammable gas consists entirely of a mixture of R152a and R32.
 12. Apropellant filling apparatus (10) of claim 3 wherein the flammable gascomprises at least 95% by weight of a mixture of R152a and R32.
 13. Apropellant filling apparatus (10) of claim 3 wherein the flammable gascomprises at least 98% by weight of a mixtures of R152a and R32.
 14. Apropellant filling apparatus (10) of claim 3 wherein the flammable gascomprises at least 99% by weight of a mixtures of R152a and R32.
 15. Apropellant filling apparatus (10) of claim 1 wherein the propellant hasa global warming potential (GWP) of below
 1000. 16. A propellant fillingapparatus (10) of claim 1 wherein the propellant has a global warmingpotential (GWP) of below
 700. 17. A propellant filling apparatus (10) ofclaim 1 wherein the propellant has a global warming potential (GWP) ofbelow
 150. 18. A propellant filling apparatus (10) of claim 1 whereinthe propellant includes one or more of the following: solvents,surfactants, lubricants, excipients.
 19. A propellant filling apparatus(10) of claim 1 supplying in use a said inert gas wherein the inert gasis nitrogen.
 20. A propellant filling apparatus (10) of claim 1 whereinthe oxygen threshold level of oxygen triggering circulation of inert gaswithin the filling booth (11) is 9.8%.
 21. A propellant fillingapparatus (10) of claim 1 wherein the oxygen threshold level of oxygentriggering circulation of inert gas within the filling booth (11) is7.8%.
 22. A propellant filling apparatus (10) of claim 1 wherein theapparatus further comprises a controller for controlling the temperatureof the inert gas supply.
 23. A propellant filling apparatus (10) claim 1wherein the apparatus further comprises a controller for controlling thehumidity of the inert gas supply.
 24. A propellant filling apparatus(10) of claim 1 including a pressure controller (23) that controls thespeed of the extraction fan (17), the pressure controller (23) measuringgas pressure in the filling booth (11) and comparing it with atmosphericpressure.
 25. A propellant filling apparatus (10) of claim 1 wherein thefilling apparatus satisfies “current good manufacturing practices”(cGMP) requirements.
 26. A method of operating a propellant fillingapparatus (10), the method comprising the steps of filling one or morecontainers in a filling booth (11) with a propellant; supplying an inertgas into the filling booth (11); adjusting the fan speed of anextraction fan (17) to maintain a lower pressure in the filling booth(11) as compared to atmospheric pressure outside the filling booth (11);detecting levels of oxygen in the filling booth (11); and circulatingthe inert gas in the filling booth (11) when the detected level ofoxygen in the filling booth (11) attains or exceeds a threshold levelcorresponding to the maximum oxygen concentration of the propellant. 27.The method of operating a propellant filling apparatus (10) of claim 26wherein the method further comprises the step of detecting the level ofinert gas in the filling booth (11).
 28. The method of operating apropellant filling apparatus (10) of claim 26 wherein the propellant isDifluoroethane (R152a).
 29. The method of operating a propellant fillingapparatus (10) of claim 26 wherein the threshold level of oxygentriggering circulation within the filling booth (11) is 9.8%.
 30. Themethod of operating a propellant filling apparatus (10) of claim 26wherein the threshold level of oxygen triggering circulation within thefilling booth (11) is 7.8%.
 31. A method of operating a propellantfilling apparatus (10) when carried out using an apparatus (10)comprising a filling booth (11) for receiving within it one or morecontainers for filling with a propellant; a propellant inlet (12) to thefilling booth (11) that is capable of supplying propellant, for filinginto one or more containers within the filling booth (11), from apropellant supply; an inert gas inlet (13) supplying inert gas from aninert gas supply (14) into the filling booth (11); a discharge outlet(16) from the filling booth (11); an extraction fan (17) that is capableof adjusting its fan speed to maintain the pressure of gas in thefilling booth (11) to be lower than atmospheric pressure outside thefilling booth (11); and an oxygen detector (27) that is capable ofdetecting levels of oxygen in the filling booth (11) and triggeringcirculation of inert gas in the filling booth (11) when the level ofoxygen in the filling booth attains or exceeds an oxygen threshold levelthat is proportional to the maximum oxygen concentration of thepropellant.